Pediatrics

Aleem, S., Robbins, C., Murphy, B., Elliott, S., Akinyemi, C., Paredes, N., Tolia, V.N., Zimmerman, K.O., Goldberg, R.N., Benjamin, D.K. and Greenberg, R.G. (2021). “The use of supplemental hydrocortisone in the management of persistent pulmonary hypertension of the newborn.” J Perinatol Feb 15. [Epub ahead of print].

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OBJECTIVE: Characterize association between hydrocortisone receipt and hospital outcomes of infants with persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: Cohort study of infants ≥34 weeks with PPHN who received inhaled nitric oxide at <7 days of age (2010-2016). We generated propensity scores, and performed inverse probability-weighted regression to estimate hydrocortisone effect on outcomes: death, chronic lung disease (CLD), oxygen at discharge. RESULTS: Of 2743 infants, 30% received hydrocortisone, which was associated with exposure to mechanical ventilation, sedatives, paralytics, or vasopressors (p < 0.001). There was no difference in death, CLD, or oxygen at discharge. In infants with meconium aspiration syndrome, hydrocortisone was associated with decreased oxygen at discharge (odds ratio 0.56; 95% confidence interval 0.21, 0.91). CONCLUSIONS: There was no association between hydrocortisone receipt and death, CLD, or oxygen at discharge in our cohort. Prospective studies are needed to evaluate the effectiveness of hydrocortisone in infants with PPHN.

Schwarz, B.C., Godwin, W.J., Wayson, M.B., Dewji, S.A., Jokisch, D.W., Lee, C. and Bolch, W.E. (2020). “Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal photon sources.” Phys Med Biol Nov 3. [Epub ahead of print].

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Assessment of radiation absorbed dose to internal organs of the body from the intake of radionuclides or, in the medical setting through the injection of radiopharmaceuticals, is generally performed based upon reference biokinetic models or patient imaging data, respectively. Biokinetic models estimate the time course of activity localized to source organs. The time-integration of these organ activity profiles are then scaled by the radionuclide S value, which defines the absorbed dose to a target tissue per nuclear transformation in various source tissues. S values are computed using established nuclear decay information (particle energies and yields), and a parameter termed the specific absorbed fraction (SAF). The SAF is the ratio of the absorbed fraction (AF) – fraction of particle energy emitted in the source tissue that is deposited in the target tissue – and the target organ mass. While values of the SAF may be computed using patient-specific or individual-specific anatomic models, they have been more widely available through the use of computational reference phantoms. In this study, we report on an extensive series of photon SAFs computed in a revised series of the UF/NCI pediatric reference phantoms which have been modified to conform to the specifications embodied in the ICRP reference adult phantoms of Publication 110 (e.g., organs modeled, organ ID numbers, blood contribution to elemental compositions). Following phantom anatomical revisions, photon radiation transport simulations were performed using MCNPX v2.7 in each of the 10 phantoms of the series – male and female newborn, 1-year-old, 5-year-old, 10-year-old, and 15-year-old – for 44 different source and target tissues. A total of 25 photon energies were considered from 10 keV to 10 MeV along a logarithm energy grid. Detailed analyses were conducted of the relative statistical errors in the Monte Carlo target tissue energy deposition tallies at low photon energies and over all energies for source-target combinations at large intra-organ separation distances. Based on these analyses, various data smoothing algorithms were employed, including multi-point weighted data smoothing, and log-log interpolation at low energies (1 and 5 keV) using limiting SAF values based upon target organ mass to bound the interpolation interval. The final dataset is provided in a series of 10 electronic annexes in MS Excel format. The results of this study were further used as the basis for assessing the radiative component of internal electron source SAFs as described in our companion paper for this same pediatric phantom series.

Schwarz, B.C., Godwin, W.J., Wayson, M.B., Dewji, S.A., Jokisch, D.W., Lee, C. and Bolch, W.E. (2020). “Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal electron sources.” Phys Med Biol Nov 3. [Epub ahead of print].

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In both the ICRP and MIRD schemata of internal dosimetry, the S-value is defined as the absorbed dose to a target organ per nuclear decay of the radionuclide in a source organ. Its computation requires data on the energies and yields of all radiation emissions from radionuclide decay, the mass of the target organ, and the value of the absorbed fraction – the fraction of particle energy emitted in the source organ that is deposited in the target organ. The specific absorbed fraction (SAF) is given as the ratio of the absorbed fraction and the target mass. Historically, in the early development of both schemata, computational simplifications were made to the absorbed fraction in considering both organ self-dose (r_S=r_T) and organ cross-dose (r_S≠r_T). In particular, the value of the absorbed fraction was set to unity for all “non-penetrating” particle emissions (electrons and alpha particles) such that they contributed only to organ self-dose. As radiation transport codes for charged particles became more widely available, it became increasingly possible to abandon this distinction and to explicitly consider the transport of internally emitted electrons in a manner analogous to that for photons. In this present study, we report on an extensive series of electron SAFs computed in a revised series of the UF/NCI pediatric phantoms. A total of 28 electron energies – 0 to 10 MeV – along a logarithmic energy grid are provided in electronic annexes, where 0 keV is associated with limiting values of the SAF. Electron SAFs were computed independently for collisional energy losses (SAFCEL) and radiation energy losses (SAFREL) to the target organ. A methodology was employed in which values of SAFREL were compiled by first assembling organ-specific and electron energy-specific bremsstrahlung x-ray spectra, and then using these x-ray spectra to re-weight a previously established monoenergetic database of photon SAFs for all phantoms and source-target combinations. Age-dependent trends in the electron SAF were demonstrated for the majority of the source-target organ pairs, and were consistent to values given for the ICRP adult phantoms. In selected cases, however, anticipated age-dependent trends were not seen, and were attributed to anatomical differences in relative organ positioning at specific phantom ages. Both the electron SAFs of this study, and the photon SAFs from our companion study, are presently being used by ICRP Committee 2 in its upcoming pediatric extension to ICRP Publication 133.

Ahmad, K. A., M. M. Bennett, S. E. Juul, R. K. Ohls, R. H. Clark and V. N. Tolia (2019). “Utilization of Erythropoietin within the United States Neonatal Intensive Care Units from 2008 to 2017.” Am J Perinatol Dec 13. [Epub ahead of print].

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OBJECTIVE: Little data are available regarding erythropoietin (Epo) utilization patterns within neonatal intensive care units (NICUs). We sought to describe the trends in Epo utilization across a large cohort of U.S. NICUs. STUDY DESIGN: This is a retrospective cohort study of infants discharged from 2008 to 2017 using the Pediatrix Clinical Data Warehouse. RESULTS: We identified 704,159 eligible infants from 358 sites, of whom 9,749 (1.4%) had Epo exposure. For extremely low gestational age newborns (ELGANs), Epo exposure ranged from 7.6 to 13.5%. We found significant site variability in Epo utilization in ELGANs. Among the 299 NICUs caring for ELGANs during the study period, 184 (61.5%) never used Epo for this population, whereas 21 (7%) utilized Epo in 50% or more of eligible infants. Epo was initiated at a median of 25 days in ELGANs. For infants with hypoxic-ischemic encephalopathy (HIE), Epo exposure remained

van der Knaap, M. S., R. Schiffmann, F. Mochel and N. I. Wolf (2019). “Diagnosis, prognosis, and treatment of leukodystrophies.” Lancet Neurol Jul 12. [Epub ahead of print].

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Leukodystrophies comprise a large group of rare genetic disorders primarily affecting CNS white matter. Historically, the diagnostic process was slow and patient prognosis regarded as poor because curative treatment was only available for very few leukodystrophies in early stages of the disease. Whole-exome sequencing has both greatly increased the number of known leukodystrophies and improved diagnosis. Whether MRI keeps its central place in diagnosis and what the role is of whole-exome sequencing are relevant questions for neurologists. Improved diagnosis has revealed the phenotypic variability of leukodystrophies, requiring adaptation of prognostication. Technological advance in molecular techniques and improved insight into the pathophysiology of individual leukodystrophies have led to therapeutic developments, including drug design and gene therapy. Despite this progress, therapies are only beneficial early in the disease course, emphasising the need for a speedy diagnosis and for research on regenerative approaches to repair the damage already present.